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Alcohol. 2017 Jun;61:51-61. doi: 10.1016/j.alcohol.2017.01.014. Epub 2017 May 18.

Maternal alcohol exposure during mid-pregnancy dilates fetal cerebral arteries via endocannabinoid receptors.

Author information

1
Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN, USA.
2
Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, Memphis, TN, USA.
3
Department of Comparative Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
4
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA.
5
Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN, USA. Electronic address: abukiya@uthsc.edu.

Abstract

Prenatal alcohol exposure often results in fetal alcohol syndrome and fetal alcohol spectrum disorders. Mechanisms of fetal brain damage by alcohol remain unclear. We used baboons (Papio spp.) to study alcohol-driven changes in the fetal cerebral artery endocannabinoid system. Pregnant baboons were subjected to binge alcohol exposure via gastric infusion three times during a period equivalent to the second trimester of human pregnancy. A control group was infused with orange-flavored drink that was isocaloric to the alcohol-containing solution. Cesarean sections were performed at a time equivalent to the end of the second trimester of human pregnancy. Fetal cerebral arteries were harvested and subjected to in vitro pressurization followed by pharmacological profiling. During each alcohol-infusion episode, maternal blood alcohol concentrations (BAC) reached 80 mg/dL, that is, equivalent to the BAC considered legal intoxication in humans. Circulating anandamide (AEA) and 2-arachidonoylglycerol (2-AG) remained unchanged. Ultrasound studies on pregnant mothers revealed that fetal alcohol exposure decreased peak systolic blood velocity in middle cerebral arteries when compared to pre-alcohol levels. Moreover, ethanol-induced dilation was observed in fetal cerebral arteries pressurized in vitro. This dilation was abolished by the mixture of AM251 and AM630, which block cannabinoid receptors 1 and 2, respectively. In the presence of AM251, the cannabinoid receptor agonist AEA evoked a higher, concentration-dependent dilation of cerebral arteries from alcohol-exposed fetuses. The difference in AEA-induced cerebral artery dilation vanished in the presence of AM630. CB1 and CB2 receptor mRNA and protein levels were similar in cerebral arteries from alcohol-exposed and control-exposed fetuses. In summary, alcohol exposure dilates fetal cerebral arteries via endocannabinoid receptors and results in an increased function of CB2.

KEYWORDS:

Baboon pregnancy; Binge drinking during pregnancy; Fetal alcohol exposure; Fetal cerebral artery; Maternal alcohol consumption

PMID:
28554529
PMCID:
PMC5517095
DOI:
10.1016/j.alcohol.2017.01.014
[Indexed for MEDLINE]
Free PMC Article

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